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Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells

INTRODUCTION: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP(6)) is enriched in rice bran and possesses many beneficial effects. In the pre...

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Autores principales: Pandurangan, Ashok Kumar, Ismail, Salmiah, Esa, Norhaizan Mohd, Munusamy, Murugan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209706/
https://www.ncbi.nlm.nih.gov/pubmed/30393482
http://dx.doi.org/10.5114/aoms.2018.76935
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author Pandurangan, Ashok Kumar
Ismail, Salmiah
Esa, Norhaizan Mohd
Munusamy, Murugan A.
author_facet Pandurangan, Ashok Kumar
Ismail, Salmiah
Esa, Norhaizan Mohd
Munusamy, Murugan A.
author_sort Pandurangan, Ashok Kumar
collection PubMed
description INTRODUCTION: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP(6)) is enriched in rice bran and possesses many beneficial effects. In the present study the effect of IP6 on autophagy-mediated death by modulating the mTOR pathway in HT-29 colon cancer cells was studied. MATERIAL AND METHODS: Autophagy was assessed by acridine orange (AO) staining, transmission electron microscopy, and western blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was also analyzed by western blotting. Apoptosis was analyzed by annexin V staining. RESULTS: Incubation of cells with IP(6) resulted in downregulation of the p-Akt at 3h. Along with that confocal microscopic analysis of p-AKT, IP(6) administration resulted that a diminished expression of p-Akt. mTOR pathway regulates autophagy and incubation with IP6 to HT-29 cells showed decreased expression of p-70S6Kinase, 4-EBP-1 in a time-dependent manner. Inositol-6 phosphate (10 μg/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO staining and transmission electron microscopy. We also found increased expression of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP(6). Furthermore, IP(6) induced apoptosis, as revealed by annexin V staining. CONCLUSIONS: Our results clearly indicate that IP6 induces autophagy by inhibiting the Akt/mTOR pathway.
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spelling pubmed-62097062018-11-02 Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells Pandurangan, Ashok Kumar Ismail, Salmiah Esa, Norhaizan Mohd Munusamy, Murugan A. Arch Med Sci Basic Research INTRODUCTION: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP(6)) is enriched in rice bran and possesses many beneficial effects. In the present study the effect of IP6 on autophagy-mediated death by modulating the mTOR pathway in HT-29 colon cancer cells was studied. MATERIAL AND METHODS: Autophagy was assessed by acridine orange (AO) staining, transmission electron microscopy, and western blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was also analyzed by western blotting. Apoptosis was analyzed by annexin V staining. RESULTS: Incubation of cells with IP(6) resulted in downregulation of the p-Akt at 3h. Along with that confocal microscopic analysis of p-AKT, IP(6) administration resulted that a diminished expression of p-Akt. mTOR pathway regulates autophagy and incubation with IP6 to HT-29 cells showed decreased expression of p-70S6Kinase, 4-EBP-1 in a time-dependent manner. Inositol-6 phosphate (10 μg/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO staining and transmission electron microscopy. We also found increased expression of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP(6). Furthermore, IP(6) induced apoptosis, as revealed by annexin V staining. CONCLUSIONS: Our results clearly indicate that IP6 induces autophagy by inhibiting the Akt/mTOR pathway. Termedia Publishing House 2018-07-05 2018-10 /pmc/articles/PMC6209706/ /pubmed/30393482 http://dx.doi.org/10.5114/aoms.2018.76935 Text en Copyright: © 2018 Termedia & Banach http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Basic Research
Pandurangan, Ashok Kumar
Ismail, Salmiah
Esa, Norhaizan Mohd
Munusamy, Murugan A.
Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
title Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
title_full Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
title_fullStr Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
title_full_unstemmed Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
title_short Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated death in HT-29 colon cancer cells
title_sort inositol-6 phosphate inhibits the mtor pathway and induces autophagy-mediated death in ht-29 colon cancer cells
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209706/
https://www.ncbi.nlm.nih.gov/pubmed/30393482
http://dx.doi.org/10.5114/aoms.2018.76935
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